title: Genomic profile of 320 uveal melanoma cases: chromosome 8p-loss and metastatic outcome.
abstract: OBJECTIVE
  Uveal melanoma (UM) was a fatal malignancy in 40% to 50% of cases. The aim of this study is to evaluate the independent contributions of chromosome 1, 3, 6, and 8 abnormalities for prognostication of metastasis, and to define multichromosome copy number aberration (CNA) signatures that can be used to evaluate risk.
  
  
  METHODS
  A series of 320 UM were analyzed for chromosome 1, 3, 6, and 8 abnormalities using whole genome single-nucleotide polymorphism arrays. Results for changes in six chromosomal regions were analyzed using univariate and multivariate Cox proportional hazard modeling to identify significant predictors of metastasis and CNA signatures.
  
  
  RESULTS
  Univariate Cox analysis indicated that losses of chromosome 3, 1p, 6q, and 8p and gain of 8q, as well as sex, source of tumor tissue (fine-needle aspiration biopsy [FNAB] compared with tumor from an enucleated eye), tumor basal diameter and height, and ciliary body involvement were all significant predictors of poor metastatic outcome. In the multivariate analysis, loss of chromosome 3 and 8p remained significant after adjusting for the effects of all other variables, as did sex, tissue source, and basal diameter. Multivariate analysis of the joint effects of changes in the six chromosomal regions showed that six signatures, including chromosome 3-loss, 1p-loss, 8p-loss, and/or 8q-gain had hazard ratios (HR) ranging from 7.90 to 37.25.
  
  
  CONCLUSIONS
  In UM, tumor size and location, tissue source, and sex were all significantly associated with increased metastasis. In addition, chromosome 3-loss and 8p-loss were found to be independent predictors of poor metastatic outcome and CNA signatures were identified that can add a specific HR value for classification of risk categories.
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Ewens
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.forename: Jennifer
authors.initials: J
authors.lastname: Richards-Yutz
authors.forename: Saad
authors.initials: S
authors.lastname: Al-Dahmash
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: De Luca
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Bianciotto
authors.forename: Carol L
authors.initials: CL
authors.lastname: Shields
authors.forename: Arupa
authors.initials: A
authors.lastname: Ganguly
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle; D002648:Child; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D055815:Young Adult; D000098943:Uveal Melanoma
chemical_list: D004247:DNA
keywords: SNP arrays; chromosome changes; marker; prognosis; uveal melanoma